Fri Mar 25 2022

59 articles - From Saturday Mar 19 2022 to Friday Mar 25 2022

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Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…


Meta-analysis

meta-analyses and systematic reviews


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Early administration of COVID-19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy.

The relative benefit of high titer CCP was confirmed in multivariable Cox regression. Administration of CCP with high titer antibody content determined by live viral neutralization assay to non-intubated patients is associated with modest clinical efficacy. Although shown to be only of modest clinical benefit, CCP may play a role in the future should viral variants develop that are not neutralized by other available therapeutics.

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Long-term eltrombopag for bone marrow failure depletes iron.

Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron deficiency anemia mimicking relapse, responsive to iron supplementation.

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The Registry Data Analysis of HSCT on Systemic Chronic Active EBV Infection Patients in Japan.

Notably, 79% of radiotherapy doses were less than 6 Gy. Regardless of the presence of HLH, the group with a high sIL2-R level (=2000 U/mL) showed a poorer prognosis. Although allo-HSCT is the only curative therapy for sCAEBV, treatment strategies need to be improved for high-risk patients, especially those with high levels of sIL-2R.

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Ann Oncol

Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

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Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

CtDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

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Tumor budding is an independent prognostic factor in stage III colon cancer patients: A post-hoc analysis of the IDEA-France phase III trial (PRODIGE-GERCOR).

Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized healthcare in this setting.

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Blood

Concurrent CDX2 cis-deregulation and UBTF-ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL.

This early resistance to treatment translated into a significantly higher cumulative incidence of relapse (75.0% versus 32.4%, P=0.004) in univariate and multivariate analyses. In conclusion, we discovered a novel B-ALL entity defined by the unique combination of CDX2 cis-deregulation and UBTF::ATXN7L3 fusion, representing a high-risk disease in young adults. Study can be found on NCT00327678 and NCT02617004.

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GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany.

While NRM was largely driven by infections subsequent to prolonged neutropenia and/or severe neurotoxicity and significantly higher with axi-cel, significant risk factors for PFS on multivariate analysis included bridging failure, elevated LDH, age, and tisa-cel use. In conclusion, this study suggests that important outcome determinants of CD19-directed CAR-T cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR-T cell therapy strategies.

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High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcome.

Pharmacological blockade of the canonical BMP signaling pathway significantly decreased CNS infiltration and consistently resulted in amelioration of clinical parameters including neurological score. Mechanistically, BMP4 favored chemoresistance, enhanced adhesion and migration through brain vascular endothelial cells, and promoted a pro-inflammatory microenvironment and CNS angiogenesis. These data provide evidence that BMP4 expression levels in leukemic cells could be a useful biomarker to identify children with poor outcome in the low/intermediate risk groups of BCP-ALL, and that BMP4 could be a new therapeutic target to blockade leukemic CNS disease.

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Long Term Follow-up for the Development of Subsequent Malignancies in Patients Treated with Genetically Modified IEs.

Replication competent retrovirus testing of peripheral blood mononuclear cells was negative in the 13 patients with subsequent malignancies tested. Rates of subsequent malignancy were low and comparable to standard chemotherapy. These results suggest that the administration of IECs genetically modified with gamma retroviral vectors does not increase the risk for subsequent malignancy.

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Response-adapted anti-PD1 based salvage therapy for Hodgkin lymphoma with nivolumab +/- ICE (NICE).

Among the 33 patients who bridged directly to AHCT after protocol therapy, the 2-year PFS was 94% (95%CI:78-98). PET-adapted sequential salvage therapy with Nivo or Nivo+NICE was well-tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This Clinical Trial is registered under NCT03016871.

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Soluble uric acid inhibits ß2 integrin-mediated neutrophil recruitment in innate immunity.

In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.

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Targeting platelet-derived CXCL12 impedes arterial thrombosis.

An improved variant of this peptide, i[VREY]4, binds to CXCL12 in a complex with CXCR4 on the surface of activated platelets, thereby inhibiting Btk activation and preventing platelet CXCL12-dependent arterial thrombosis. In contrast to standard anti-platelet therapies such as aspirin or P2Y12-inhibiton, i[VREY]4 reduced CXCL12-induced platelet aggregation and yet did not prolong in vitro bleeding time. We provide evidence that platelet-derived CXCL12 is involved in arterial thrombosis and can be specifically targeted by peptides that harbor potential therapeutic value against atherothrombosis.

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Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study.

After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials. gov as NCT03206970.

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Blood Adv

A bitesize introduction to canine hematologic malignancies.

An overview of standard of care therapies for each of these diseases is also provided. As comparative oncology gains recognition as a valuable setting to investigate the pathogenesis of neoplasia and to provide powerful, clinically relevant, immune competent models for the evaluation of novel therapies, the number of clinicians and scientists participating in cancer research involving dogs is expected to increase. This review aims at providing an introductory overview of canine hematologic malignancies.

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A single-arm pilot study of a mobile health exercise intervention (GO-EXCAP) in older patients with myeloid neoplasms.

In qualitative analyses, three themes were identified including positive experience with the intervention, social interactions, and flexibility. The GO-EXCAP intervention is feasible and usable for older patients with myeloid neoplasms undergoing outpatient chemotherapy. This trial is registered at as NCT04035499.

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Deep sequencing in CD34+ cells from peripheral blood allows sensitive detection of measurable residual disease in AML.

In both assays, MRD detection was superior using PB versus BM for CD34+ enrichment. Importantly, NGS on CD34+ PB cells enabled prediction of molecular relapse with high sensitivity (100%) and specificity (91%), and significantly earlier (median 48 days, range 0-281; P=0.0011) than by CD34+ DC or NGS of unsorted PB, providing additional time for therapeutic intervention. Moreover, panel sequencing in CD34+ cells allowed the early assessment of clonal trajectories in hematological complete remission.

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Prevalence of Heavy Chain MGUS by Race and Family History Risk Groups Using a High Sensitivity Screening Method.

MALDI-TOF MGUS prevalence was higher in the AA (16.5% [95%CI: 12.2%, 20.8%]) and FDR (18.3% [95%CI: 16.6%, 21.6%]) than in EA (10.8% [95%CI: 8.8%, 12.7%]) translating to prevalence ratios of 1.73 [95% CI: 1.31, 2.29] and 1.90 [95% C: 1.55, 2.34], respectively. MALDI-TOF EA prevalence was over 3-fold higher than conventional estimates but showed similar age trends. Thus, the MALDI-TOF assay found greater absolute numbers with MGUS but similar relative differences by race, family history and age as prior studies.

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Whole genome sequences discriminate hereditary hemorrhagic telangiectasia phenotypes by non-HHT deleterious DNA variants.

In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to HHT vessels had more CADD-deleterious variants in platelet (Spearman =0.25, p=0.008) and coagulation (Spearman =0.21, p=0.024) genes. However, the HHT cohort had 60% fewer deleterious variants in platelet and coagulation genes than expected (Mann Whitney p=0.021). In conclusion, HHT patients commonly have rare variants in genes of relevance to their phenotype, offering new therapeutic targets and opportunities for informed, personalised medicine strategies.

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Blood Cancer J

Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases.

At presentation, abnormal karyotype, excluding -Y, was associated with older age (p=0.04), higher leukocyte count (p=0.03) and arterial thrombosis history (p=0.02); no associations were apparent for JAK2/CALR/MPL mutations whereas ASXL1 mutations clustered with normal karyotype/-Y and TP53 with abnormal karyotype. Survival was significantly shorter in patients with abnormal karyotype or -Y, compared to those with normal karyotype (median 12, 10, and 21 years, respectively; p 60 years remained significant, along with SF3B1/SRSF2/U2AF1/TP53 mutations (p=0.04; HR 2.9), when the latter was included in the multivariable model. The current study suggests prognostic relevance for karyotype in ET.

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Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets.

SG membership superseded other prognostic factors (Rai Staging, IGHV Status) and were prognostic for response to modern (BTK inhibition) and older CLL therapies. SGs and PFGs membership provided novel drug targets and defined optimal candidates for Watch and Wait vs early intervention. Collectively proteomics demonstrates promise for improving classification, therapeutic strategy selection, and identifying novel therapeutic targets.

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Treatment patterns and outcomes according to cytogenetic risk stratification in patients with multiple myeloma: a real-world analysis.

In the absence of biomarker-driven therapy, treatment patterns remain similar across LoT in high-risk, t(11;14)+, and standard-risk subgroups. Across al LoT, patient outcomes in the high-risk subgroup were less favorable than those in the t(11;14)+ and standard-risk subgroups. Thus, there is an opportunity for novel therapeutics targeted to t(11;14) and other defined subgroups to personalize MM therapy and optimize patient outcomes.

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Haematologica

Autologous stem cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study.

In the multivariate analysis, first-line ASCT was associated with significantly prolonged PFS (HR 0.57, 95% CI 0.35-0.93) and OS (HR 0.57, 95% CI 0.33-0.99). In conclusion, our study supports the use of ASCT as a consolidation strategy for patients with PTCL in CR1. These results should be confirmed in a prospective randomized study.

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Cell-free DNA sequencing as a potential screening tool for phase I targeted treatment in refractory/relapse diffuse large B cell lymphoma.

Not available.

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Mature T-cell neoplasms and stem cell transplant: the never-ending story.

Not available.

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J Hematol Oncol

Determinants of SARS-CoV-2 waning immunity in allogeneic hematopoietic stem cell transplant recipients.

Seventy-two percent (96/133) of patients retained protective antibody levels at 6 months. Immunosuppressive drugs and low lymphocyte counts in peripheral blood correlated with lower IgG(S-RBD) titers at 6 months. Four patients (3%) developed PCR-documented SARS-CoV-2 infection and one died.

Pubmed   Journal   ReadQx   PMC

In situ antigen modification-based target-redirected universal chimeric antigen receptor T (TRUE CAR-T) cell therapy in solid tumors.

The fusogenic nanoparticle-based in situ antigen modification overcome the limitation of target antigens paucity and heterogeneity in solid tumors, improving the efficacy and broadening the applications of CAR-T cells, thus establishing a novel TRUE CAR-T cell therapeutic modality with universal application and translational potential in immunotherapies for solid tumors.

Pubmed   Journal   ReadQx   PMC

Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy.

Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of a-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.

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Leukemia

Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades; a Nordic population-based cohort study.

Age =10 years, T-cell immunophenotype, bone-marrow involvement, early and very early relapse, hypodiploidy, and Down syndrome al independently predicted worse outcome after relapse. Improvements in the primary treatment of childhood ALL has resulted in fewer relapses. However, failure to improve outcome of remaining relapses suggests a selection of harder-to-cure relapses and calls for new therapeutic strategies.

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Thromb Haemost

Early rhythm control and the risks of ischaemic stroke, heart failure, mortality and adverse events when performed early (<3 months).

Early rhythm control, especially when performed earlier (<3months), was associated with a lower risk of adverse events than usual care among patients with early AF.

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HemosIL VWF:GPIbR assay has a greater sensitivity than VWF:RCo technique to detect acquired von Willebrand syndrome in myeloproliferative neoplasms.

Evaluation of VWF Act using VWF GPIbR has a greater sensitivity compared to aggregometry to detect AVWS in T-MPNs patients.

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Pentosan polysulfate inhibits attachment and infection by SARS-CoV-2 in vitro: insights into structural requirements for binding.

Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using NMR spectroscopy and LC-MS, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective at inhibiting cell infection than low molecular weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

3-year CheckMate743 outcomes: ringing in immunotherapy for the treatment of malignant pleural mesothelioma.

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Blood

CDX2 and IDH1/2: new potential players in ALL.

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Do CARs finally hit the CLL road?

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It takes guts to boost platelet reactivity and inflammation.

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Telomere biology disorders: ends and (genetic) means.

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The many facets of liquid biopsies in lymphoma.

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Blood Cancer J

Extramedullary disease in multiple myeloma: a systematic literature review.

Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.

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CA Cancer J Clin

Cancer risk among World Trade Center rescue and recovery workers: A review.

Importantly, another study found that WTC-exposed rescue and recovery workers who are enrolled in the federally funded medical monitoring and treatment program experienced improved survival post-cancer diagnosis compared with New York state patients with cancer. On the basis of these combined cohort studies, the full effect of WTC exposure on cancer risk is becoming clearer. Consequently, the authors believe that surveillance of those with WTC exposure should be continued, and in-depth analysis of epidemiologic, molecular, and clinical aspects of specific cancers in these workers should be pursued.

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Modern developments in germline pharmacogenomics for oncology prescribing.

This review is focused on key new pharmacogenomic evidence and oncology-specific dosing recommendations. Personalized oncology care through integrated pharmacogenomics represents a unique multidisciplinary collaboration between oncologists, laboratory science, bioinformatics, pharmacists, clinical pharmacologists, and genetic counselors, among others. The authors posit that expanded consideration of germline genetic information can further transform the safe and effective practice of oncology in 2022 and beyond.

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J Hematol Oncol

Altered pathways and targeted therapy in double hit lymphoma.

Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.

Pubmed   Journal   ReadQx   PMC

Cancer vaccines as promising immuno-therapeutics: platforms and current progress.

Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

COVID-19 mRNA-1273 vaccine induces production of vaccine-induced immune thrombotic thrombocytopenia antibodies.

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COVID-19 Thromboembolism Incidence, Risk Factors and Anticoagulation Practices from a Chicago Metropolitan US Population.

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Intensive Chemotherapy for Acute Myeloid Leukemia Relapse after Allogeneic Hematopoietic Cell Transplantation.

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Real-world experience with venetoclax and hypomethylating agents in myelodysplastic syndromes with excess blasts.

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Repeated infusions of escalating doses of expanded and activated autologous natural killer cells in minimal residual disease-positive Ph+ acute lymphoblastic leukemia patients. A GIMEMA phase 1 trial.

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SARS-CoV-2 vaccination in patients with paroxysmal nocturnal hemoglobinuria: an Italian multicenter survey.

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Ann Oncol

Adding a platinum agent to neoadjuvant chemotherapy for triple-negative breast cancer: the die has not been cast.

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Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

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Risk of MDS/AML with the addition of neoadjuvant carboplatin to standard chemotherapy for triple negative breast cancer.

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J Hematol Oncol

A four-stage model for murine natural killer cell development in vivo.

These four NK cell populations are phenotypically distinct based on their expression of cell surface markers, transcription factors, and effector molecules. Using a differentiation assay ex vivo and adoptive transfer model in vivo, we confirmed that NK cell development follows our predicted four-stage model. Taken together, our findings establish two distinct populations of immature NK cells and define a model for mouse NK cell development.

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Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR-192-5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment.

Mechanistically, the oncogenic factor LIF was aberrantly elevated in HCC tissues and down-regulated by SM in HCC cells, as well as subsequently the overexpression of LIF could restore the anti-HCC effects of SM via miR-192-5p/CYR61/Akt signaling pathways. Additionally, SM could repolarize tumor associated macrophages by LIF/p-Stat3 to inhibit the growth and epithelial-mesenchymal transition of HCC, and simultaneously affected other immune cell populations in the immune (tumor) microenvironment by regulating macrophages, such as MDSCs, DCs and T cell populations. Together, these findings exploit the potential use of SM against HCC and shed light on exploring SM as a potent candidate drug for the future HCC therapeutics.

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Others

all remaining publications eg case reports, images of the month, etc…

Blood

Annexin A1- but CD10+ hairy cell leukemia.

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Zheng W, Wei J, Zebley CC, et al. Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL. Blood. 2021;138(2):122-135.

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Blood Adv

Deferasirox-induced robust and dose-dependent reversal of anemia in a patient with variants in the TRIB2 and ABCB6 genes.

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Lancet Haematol

Recognising inequalities in haematopoietic stem-cell transplantation and cellular therapy training.

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Leukemia

A simple algorithm with one flow cytometric MRD measurement identifies more than 40% of children with ALL who can be cured with low-intensity therapy. The ALL-MB 2008 trial results.

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